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Undernutrition is a public health challenge in sub-Saharan countries, including Uganda. In a previous randomized controlled trial (RCT) with a nutrition, hygiene and stimulation education intervention among mothers of 6 months’ old children, we found less caries in the intervention group when the children were 36 months of age. We now examined the effects of (i) the intervention on the microbiota, (ii) microbiota on caries, and (iii) the intervention and microbiota on caries. The original RCT comprised 511 mother/child pairs whereas in the current study we had access to data from 344/511 (67%) children aged 36 months. The saliva microbiota was determined using 16S rRNA gene sequencing. Carious lesions (a proxy for dental health) were identified using close-up intra-oral photographs of the upper front teeth. Statistical models were used to determine host-microbiota associations. The intervention had a significant effect on the microbiota, e.g. an increase in Streptococcus abundance and decreases in Alloprevotella and Tannerella. Significant associations between the microbiota and dental caries were identified: Positive associations of Capnocytophaga and Tannerella suggest that these taxa may be deleterious to dental health while negative associations of Granulicatella, Fusobacterium, and Abiotrophia suggest taxa potentially beneficial or benign contributors to dental health. Based on taxonomic profiles, the effects of the intervention and microbiota on dental health may be independent of one another. Educational interventions with emphasis on nutrition and oral hygiene may provide a feasible strategy to decrease progression of childhood caries in low-resource settings.

Summary Objective Verify the presence of association between four variables—transforming growth factor α (TGFA; C/T rs1523305), interferon regulatory factor 6 (IRF6; A/C rs2013162), muscle segment homeobox 1 (MSX1; A/G rs12532), and dental anomalies—with skeletal malocclusion by comparing these four variables with Angle Classes I, II, and III, and normal, hyperdivergent, and hypodivergent growth patterns. Methods A total of 505 orthodontic records of patients older than 8 years were evaluated. The sample consisted of 285 (56.4 per cent) females, 220 (43.6 per cent) males, 304 (60.2 per cent) Whites (the rest were mixed Blacks with Whites), with a mean age of 20.28 (±10.35) years (ranging from 8 to 25 years). Eight cephalometric points, which served as the anatomical framework for obtaining angles and cephalometric measurements, were used for skeletal characterization using the Dolphin Software. Samples of saliva were collected and the DNA was extracted, diluted and quantified. Markers in TGFA, IRF6, and MSX1 were used and genotypes were obtained using TaqMan chemistry. Odds ratio (OR) and 95 per cent confidence interval (CI) calculations, chi-square, Fisher’s Exact, Mann–Whitney, and correlation coefficient tests (significance level: 95 per cent) were performed. Bonferroni correction was applied and an alpha of 0.0006 was considered statistically significant. Results There was no statistically significant associations between markers in TGFA or IRF6 with skeletal malocclusions. Tooth agenesis was associated with facial convexity (P < 0.001). MSX1 was associated with Class II skeletal malocclusion (P = 0.0001, OR = 0.6, CI = 0.46–0.78). Conclusion Individuals with tooth agenesis were more likely to have a convex face. MSX1 was associated with Class II skeletal malocclusion.

Pain is an experience of a subjective nature, interpreted in a personal way and according to an extensive palette of factors unique to each individual. Orofacial pain can be acute or chronic and it is usually the main reason for the patient to seek dental care. Pain perception varies widely among individuals. This variability is considered a mosaic of factors, which include biopsychosocial factors and genetic factors. Understanding these differences can be extremely beneficial for pain management in a personalized and more efficient way. We performed association studies to investigate phenotypes associated with genetic markers in pain-related genes in two groups of patients who received more or less anesthesia during dental treatment. The study group was comprised of 1289 individuals participating in the Dental Registry and DNA Repository Project (DRDR) of the University of Pittsburgh, with 900 participants in the group that received the most anesthesia and 389 constituting the comparison group that received less anesthesia. We tested 58 phenotypes and genotypic data of seven SNPs in genes that are associated with pain perception, pain modulation and response to drugs used in pain treatment: COMT (rs4818 and rs6269), GCH1 (rs3783641), DRD2 (rs6276), OPRM1 (rs1799971), SCN9A (rs6746030) and SCN10A (rs6795970). The analysis revealed a protective effect of rs1799971 on asthma in the total sample. rs3783641 was associated with salivary secretion disorders in females who received more anesthesia. rs1799971 was also associated with periodontitis in Whites who received less anesthesia. rs4818 was associated with disease and other tongue conditions in the group composed of Blacks who received less anesthesia. In conclusion, our study implicated variants in pain-related genes in asthma and oral phenotypes.

Objectives: The purpose of this study was to determine if shear bond resistance of orthodontic brackets bonded to enamel is associated with genes implicated in the enamel mineralization process.Methods: Ninety-two permanent, caries-free premolars extracted for orthodontic purposes and their associated saliva samples were obtained. Eighteen single nucleotide polymorphisms (SNPs) were studied for association with shear bond resistance. The genes of interest in this study were those previously associated with dental caries by our group. All tooth samples were bonded on the buccal surface with metallic lower lateral brackets, and then subjected to physical debonding. The force required to debond the bracket was recorded in Newtons (N) and converted to a shear bond resistance value in Megapascals (N/mm(2)). The data were analyzed for statistical significance as compared with the mean shear bond resistance value via PLINK whole genome analysis software.Results: Associations were found between the SNPs for tuftelin (rs7526319, P = 0.004) and amelogenin (rs17878486, P = 0.04) and a higher shear bond resistance.Conclusion: The collected data support the proposed hypothesis that genes involved in the mineralization process affect the bonding of orthodontic brackets, and such an association is of value for the field of orthodontics, particularly in evaluating the efficacy of enamel-resin bond strength for patients receiving treatment. Dean's Summer Research Scholarship Program at the School of Dental Medicine, University of Pittsburgh, Pittsburgh, PA, USA

Non-carious cervical lesions (NCCLs) are characterized by a loss of hard dental tissue near the cement–enamel junction with multifactorial etiology. The aim of this study was to demonstrate that occlusal factors as attrition, malocclusion, and bruxism, and mental disorders as depression, stress, and anxiety are involved in the etiology of NCCLs. Salivary samples and clinical data of 340 individuals selected from 6,112 participants were obtained from the University of Pittsburgh School of Dental Medicine Dental Registry and DNA Repository project. The affected group was formed by individuals with NCCL (34 females, 34 males, mean age 55.34 years). In addition, the comparison group was formed by individuals without NCCL (136 females, 136 males, mean age 55.14 years). Eleven single-nucleotide polymorphisms (SNPs) previously associated with mental disorders were genotyped and tested for association with NCCLs. When all occlusal factors were combined there was found a significant association with NCCL (p = 0.000001/adjusted OR 4.38, 95% CI 2.50–7.69). Attrition (OR 3.56, 95% CI 2.00–6.32) and malocclusion (OR 5.09, 95% CI 1.65–15.68) as separate variables showed statistically significant associations with NCCL. There was a significant difference in stress history between the two groups (OR 2.17, 95% CI 1.08–4.39). No associations between NCCLs and the SNPs selected were found. However, when the occlusal factors were analyzed as covariates, associations were found between bruxism and seven of the selected SNPs. Our results suggest that occlusal factors might be associated with NCCLs.

Objectives Dental caries is a highly prevalent infectious disease that causes tooth decay. While no single bacterial species is causative of dental caries, the role of the oral microbiome in oral health and caries is gaining interest. The purpose of this study is to compare the major species present in whole saliva samples from caries‐free and caries‐active children using the IBIS Universal Biosensor. Material and Methods The abundant microbial species in ninety‐five whole saliva samples from caries‐free and caries‐active subjects were characterized using the IBIS Universal Biosensor. Results Twenty‐four genera and sixty‐five species were detected. Candida and Streptococcus were common across samples, and often the dominant genus. While we did not observe a strong association between the most abundant species and oral health, Bacteroides thetaiotaomicron and Rothia mucilaginosa were enriched in children with active caries; while, Staphylococcus epidermidis was enriched in caries‐free children. Conclusions These study trends observed suggest that microbial markers in saliva may serve as predictors of oral health and thus aid in diagnosis and treatments for prevention of caries. Consistent with competitive interactions, we also observed negative associations between Streptococcus pneumoniae and other streptococcal species, Staphylococcus aureus and S. epidermidis, Candida and Neisseria, and Saccharomyces and Streptococcus.

This study aimed to evaluate the association of genetic variants inACTN3 and MYO1H with craniofacial skeletal patterns in Brazilians.This cross-sectional study enrolled orthodontic and orthognathic patients selected from 4 regions of Brazil. Lateral cephalograms were used and digital cephalometric tracings and analyzes were performed for craniofacial phenotype determination. Participants were classified according to the skeletal malocclusion in Class I, II or III; and according to the facial type in Mesofacial, Dolichofacial or Brachyfacial. Genomic DNA was extracted from saliva samples containing exfoliated buccal epithelial cells and analyzed for genetic variants inACTN3 (rs678397 and rs1815739) and MYO1H (rs10850110) by real-time PCR. Chi-square or Fisher's exact tests were used for statistical analysis (α = 5%).A total of 646 patients were included in the present study. There was statistically significant association of the genotypes and/or alleles distributions with the skeletal malocclusion (sagittal skeletal pattern) and facial type (vertical pattern) for the variants assessed inACTN3 (P 0.05). For the genetic variant evaluated in MYO1H, there was statistically significant difference between the genotypes frequencies for skeletal Class I and Class II (P 0.05). The reported associations were different depending on the region evaluated.ACTN3 and MYO1H are associated with sagittal and vertical craniofacial skeletal patterns in Brazilian populations.

Background Dental caries is one of the most common chronic diseases and is influenced by a complex interplay of genetic and environmental factors. Most previous genetic studies of caries have focused on identifying genes that contribute to dental caries in specific ethnic groups, usually of European descent. Methods The aim of this study is to conduct a genome-wide association study (GWAS) to identify associations affecting susceptibility to caries in a large multiethnic population from Argentina, the Philippines, Guatemala, Hungary, and the USA, originally recruited for studies of orofacial clefts (POFC, N = 3686). Ages of the participants ranged from 2 to 12 years for analysis of the primary dentition, and 18–60 years for analysis of the permanent dentition. For each participant, dental caries was assessed by counts of decayed and filled teeth (dft/DFT) and genetic variants (single nucleotide polymorphisms, SNPs) were genotyped or imputed across the entire genome. Caries was analyzed separately for the primary and permanent dentitions, with age, gender, and presence/absence of any type of OFC treated as covariates. Efficient Mixed-Model Association eXpedited (EMMAX) was used to test genetic association, while simultaneously accounting for relatedness and stratification. Results We identified several suggestive loci (5 × 10−8 P −6) within or near genes with plausible biological roles for dental caries, including a cluster of taste receptor genes (TAS2R38, TAS2R3, TAS2R4, TASR25) on chromosome 7 for the permanent dentition analysis, and DLX3 and DLX4 on chromosome 17 for the primary dentition analysis. Genome-wide significant results were seen with SNPs in the primary dentition only; however, none of the identified genes near these variants have known roles in cariogenesis. Conclusion The results of this study warrant further investigation and may lead to a better understanding of cariogenesis in diverse populations, and help to improve dental caries prediction, prevention, and/or treatment in future.

Background The Met136Val mutation in SCN8A was described in a case of trigeminal neuralgia but no frequency among affected individuals was provided. Methods Direct sequencing of 123 individuals diagnosed with classic trigeminal neuralgia was performed aimed to detect the Met136Val change. Results No cases of classical trigeminal neuralgia studied had the Met136Val mutation in SCN8A. Conclusion Met136Val mutation in SCN8A is not a frequent cause of classical trigeminal neuralgia., This paper provides evidence that the SCN8A Met136Val is not a common cause of trigeminal neuralgia.

ObjectivesTo explore whether variations in odontogenesis-related genes are associated with tooth-size discrepancies.Materials and MethodsMeasurements of the width of permanent teeth were obtained from dental casts of 62 orthodontic patients (age 15.65 ± 6.82 years; 29 males and 33 females). Participants were classified according to the anterior and overall Bolton ratios as without tooth-size discrepancy or with maxillary or mandibular tooth-size excess. Genomic DNA extracted from buccal cells was used, and 13 single nucleotide polymorphisms (SNPs) across nine genes were genotyped by polymerase chain reaction using TaqMan chemistry. χ2 or Fisher exact tests were applied to determine the overrepresentation of genotypes/alleles depending on the type of tooth-size discrepancy (α = .05; corrected P value: P < 5.556 × 10−3). Odds ratios (ORs) and their correspondent 95% confidence intervals (CIs) were also calculated to investigate the risk of this phenotype for the SNPs having significant association.ResultsIndividuals carrying the FGF10 rs900379 T allele were more likely to have larger mandibular teeth (OR = 3.74; 95% CI: 1.65–8.47; P = .002). This effect appeared to be stronger when two copies of the risk allele (TT) were found (recessive model, OR = 6.16; 95% CI: 1.71–22.16; P = .006). On the other hand, FGF13 rs5931572 rare homozygotes (AA, or male A hemizygotes) had increased risk of displaying tooth-size discrepancies when compared with the common homozygotes (GG, or male G hemizygotes; OR = 10.32; 95% CI: 2.20–48.26; P = .003).ConclusionsThe results suggest that FGF10 and FGF13 may contribute to the presence of tooth-size discrepancies.

One of the biggest challenges in clinical genetics is establishing associations between specific germline mutations and the resulting spectrum of phenotypes. The careful characterization of clinical presentations continues to be a tool for establishing these genotype phenotype correlations. The authors intend, by presenting a case study, proposing that the concomitant occurrence of a combinations of mild structural anomalies in the same individual may be due to changes in genes that can be linked by related pathways. A new born with cleft lip and palate was referred at the Cleft Lip and Palate Center. The anamnese was performed and collected data of familiar history, parental consanguinity, and information about pregnancy period. The careful characterization of clinical presentations and the genetic pathways was studied. It is possible that there is no single mutation that can be clearly identified as the etiology of the combination of the defects displayed in the present case.

Summary Background & aims The symptoms of xerostomia and taste alteration are adverse effects which frequently occur in patients under chemotherapy and once associated they can potentially impair their nutritional status. The aim of this study was to investigate the association of xerostomia and taste alterations in patients being treated by neoplastic chemotherapy. Methods Fifty patients scheduled to receive neoplastic chemotherapy were followed for their first two chemotherapy cycles for solid tumors and the Chemotherapy-Induced Taste Alteration Scale (CiTAS) was adopted. Xerostomia was defined by the presence of dry mouth complaints reported by the patients and signs of hyposalivation identified during the intraoral examination. Results Of the 50 patients, 33 were women, mean age; 61,48 ± 9,07 years, and 17 were men, mean age; 57,35 ± 11,50 years. The most common tumor was located in the breast affecting 15 patients (30%). The Mann–Whitney test showed that the mean scores of CiTAS were significantly higher for those patients who reported having xerostomia when compared with those without xerostomia after the first two chemotherapy cycles. The cofounding variables such as age, smoking habits and use of antidepressants were not statistically associated with taste alterations (p > 0.05). Conclusions Taste alterations were worse for patients who complained of xerostomia during the first two cycles of antineoplastic chemotherapy and the association of both symptoms can potentially impair their nutritional status and quality of life.

International audience; Craniofacial asymmetry, mandibular condylar modeling and temporomandibular joint disorders are common comorbidities of skeletally disproportionate malocclusions, but etiology of occurrence together is poorly understood. We compared asymmetry, condyle modeling stability and temporomandibular health in a cohort of 128 patients having orthodontics and orthognathic surgery to correct dentofacial deformity malocclusions. We also compared ACTN3 and ENPP1 genotypes for association to clinical conditions. Pre-surgical posterior-anterior cephalometric and panometric radiographic analyses; jaw pain and function questionnaire and clinical examination of TMD; and SNP-genotype analysis from saliva samples were compared to assess interrelationships. Almost half had asymmetries in need of surgical correction, which could be subdivided into four distinct morphological patterns. Asymmetric condyle modeling between sides was significantly greater in craniofacial asymmetry, but most commonly had an unanticipated pattern. Often, longer or larger condyles occurred on the shorter mandibular ramus side. Subjects with longer ramus but dimensionally smaller condyles were more likely to have self-reported TMD symptoms (p = 0.023) and significantly greater clinical diagnosis of TMD (p = 0 .000001), with masticatory myalgia most prominent. Genotyping found two significant genotype associations for ACTN3 rs1671064 (Q523R missense) p = 0.02; rs678397 (intronic SNP) p = 0.04 and one significant allele association rs1815739 (R577X nonsense) p = 0.00. Skeletal asymmetry, unusual condyle modeling and TMD are common and interrelated components of many dentofacial deformities. Imbalanced musculoskeletal functional adaptations and genetic or epigenetic influences contribute to the etiology, and require further investigation.

The study of dental development in individuals born with cleft lip and palate (CLP) serves to determine when orthodontic intervention should start. Objective To evaluate the permanent second molar development in children born with cleft lip and palate according to Demirjian’s and Nolla’s methods. Methodology Out of a total of 513 digital panoramic radiographs, 113 pairs of children aged 3 to 16 years were selected. The exams were from children born with or without cleft lip and palate, of the same sex, with an age difference of up to 30 days. The images were analyzed by three examiners and reliability was checked through intra-examiner agreement by the Kappa test. The data were analyzed by Wilcoxon's and Mann-Whitney tests according to each dataset. Results The findings indicated delayed development of the permanent second molars in children with CLP (P

Cleft lip with or without cleft palate (CLP) is considered the most frequent congenital malformations of the head and neck, with cleft individuals exhibiting more chances of presenting abnormalities such as developmental defects of enamel (DDE). Matrix metallopeptidase 2 (MMP2) is a membrane-bound protein with collagen-degrading ability and has important roles in tooth formation and mineralization. The aim of this study was to evaluate the frequency, location, severity and extent of DDE found in the maxillary incisors for groups of individuals born with CLP, as well as understanding their relationship with the cleft side. Besides, this study addresses the hypothesis that DDE can be influenced by variation in theMMP2genes (rs9923304). Individual samples, clinical history, intraoral photographs and panoramic radiographs were obtained from 233 patients under treatment at the Cleft Lip and Palate Service of the University Hospital Lauro Wanderley at the Federal University of Paraíba. Digital images were examined by the same evaluator using the Classification of Defects According to the Modified DDE Index, and then loaded into the Image Tool software, where two measurements were made: total area of the buccal surface (SA) and the area of the DDE (DA), obtaining the percentage of the surface area affected (%SAD) (ICC = 0.99). Genomic DNA was extracted from saliva samples from 124 participants. Genotyping was carried out using TaqMan chemistry for one marker inMMP2(rs9923304). Statistical analyses were performed by The Jamovi Project software. The Shapiro-Wilk test was applied, followed by the Student’s t-test and the Mann-Whitney test. Chi-square and Fisher’s exact tests, and odds ratio (OR) with 95% confidence interval (CI) calculations were used to determine Hardy-Weinberg equilibrium and statistically significant differences with an alpha of 0.05. No significant differences in the prevalence and extent of enamel defects were found between male and female individuals born with CLP (p = 0.058256). The frequency of individuals presenting teeth with DDE, in relation to the cleft and non-cleft side, was statistically different (p 7.151> 10.942). However, the averages of %SAD were similar (p = 0.18). The highest means of the %SAD were found in individuals with bilateral cleft lip with or without cleft palate (BCLP) when compared to individuals with unilateral cleft lip with or without cleft palate (UCLP), for the teeth inside (IA) and outside the cleft area (OA) (p MMP2may have a role in the cases that presented DDE and genotyping rs9923304 could serve as the basis for a genomic approach to define risks for individuals born with CLP. Frequency and severity of DDE is strongly related to the CLP phenotype, since the highest values were found for BCLP. However, the extent of the DDE is independent of its relationship with the side of the cleft.

Cancer is a disease caused by a process that drives the transformation of normal cells into malignant cells. The late diagnosis of cancer has a negative impact on the health care system due to high treatment cost and decreased chances of favorable prognosis. Here, we aimed to identify orofacial conditions that can serve as potential risk markers for cancers by performing a phenome-wide scan (PheWAS). From a pool of 6,100 individuals, both genetic and epidemiological data of 1,671 individuals were selected: 350 because they were previously diagnosed with cancer and 1,321 to match to those individuals that had cancer, based on age, sex, and ethnicity serving as a comparison group. Results of this study showed that when analyzing the individuals affected by cancer separately, tooth loss/edentulism is associated with SNPs in AXIN2 (rs11867417 p = 0.02 and rs2240308 p = 0.02), and leukoplakia of oral mucosa is associated with both AXIN2 (rs2240308 p = 0.03) and RHEB (rs2374261 p = 0.03). These phenotypes did not show the same trends in patients that were not diagnosed with cancer, allowing for the conclusion that these phenotypes are unique to cases with higher cancer risk.

Background Oral hygiene instruction is an intervention widely practiced but increased knowledge about oral health does not necessarily dramatically impact oral disease prevalence in populations. We aimed to measure plaque and bleeding in periodontal patients over time to determine patterns of patient response to oral hygiene instructions. Methods Longitudinal plaque and bleeding index data were evaluated in 227 periodontal patients to determine the impact of oral hygiene instructions. Over multiple visits, we determined relative plaque accumulation and gingival bleeding for each patient. Subsequently, we grouped them in three types of oral hygiene status in response to initial instructions, using the longitudinal data over the period they were treated and followed for their periodontal needs. These patterns of oral hygiene based on the plaque and gingival bleeding indexes were evaluated based on age, sex, ethnic background, interleukin 1 alpha and beta genotypes, diabetes status, smoking habits, and other concomitant diseases. Chi-square and Fisher’s exact tests were used to determine if any differences between these variables were statistically significant with alpha set at 0.05. Results Three patterns in response to oral hygiene instructions emerged. Plaque and gingival bleeding indexes improved, worsened, or fluctuated over time in the periodontal patients studied. Out of all the confounders considered, only ethnic background showed statistically significant differences. White individuals more often than other ethnic groups fluctuated in regards to oral hygiene quality after instructions. Conclusions There are different responses to professional oral hygiene instructions. These responses may be related to ethnicity.

Made available in DSpace on 2018-12-11T16:52:03Z (GMT). No. of bitstreams: 0 Previous issue date: 2018-04-01 Objective: The goal of the present work was to use dental conditions that have been independently associated with cleft lip and palate (CL/P) as a tool to identify a broader collection of individuals to be used for gene identification that lead to clefts. Study design: We studied 1573 DNA samples combining individuals that were born with CL/P or had tooth agenesis, supernumerary teeth, molar incisor hypomineralization, or dental caries with the goal to identify genetic associations. We tested 2 single-nucleotide polymorphisms that were located in the vicinity of regions suggested to contribute to supernumerary teeth. Overrepresentation of alleles were determined for combinations of individuals as well as for each individual phenotypic group with an α of.05. Results: We determined that the allele C of rs622260 was overrepresented in all individuals studied compared with a group of unrelated individuals who did not present any of the conditions described earlier. When subgroups were tested, associations were found for individuals with hypomineralization. Conclusions: Although we did not test this hypothesis directly in the present study, based on associations reported previously, we believe that CL/P is actually a syndrome of alterations of the dentition, and considering it that way may allow for the identification of genotype-phenotype correlations that may be useful for clinical care. Department of Pedodontics School of Dentistry Istanbul University Department of Pedodontics School of Dentistry Istanbul Medipol University Department of Oral Biology University of Pittsburgh School of Dental Medicine Department of Pediatric Dentistry UNESP Department of Pediatric Dentistry University of Pittsburgh School of Dental Medicine Department of Pediatric Dentistry UNESP

The identification of clinical patterns of tooth agenesis in individuals born with craniofacial deformities may be a useful tool for risk determination of these defects. We hypothesize that specific craniofacial deformities are associated with third molar agenesis. Objective The aim of this study was to identify if third molar agenesis could have a relation with other craniofacial structure alterations, such as cleft lip and palate, skeletal malocclusion, or specific growth patterns in humans. Design Data were obtained from 550 individuals ascertained as part of studies aiming to identify genetic contributions to oral clefts. 831 dental records of patients aged over eight years seeking orthodontic treatment were also included. SN-GoGn angle were used to classify the growth pattern (hypo-divergent, normal and hyper-divergent), and the ANB angle was used to verify the skeletal malocclusion pattern (Class I, II and III). Panoramic radiographs were used to determine third molar agenesis. Results A high frequency of third molar agenesis among individuals born with cleft lip with or without cleft palate (55%), as well as among their relatives (93.5%) was found. Third molar agenesis was not associated to skeletal malocclusion or growth pattern. Conclusion It appears that third molar agenesis is associated with the disturbances that lead to cleft lip and palate.

Dental caries is a multifactorial infectious disease and a major public health problem estimated to affect 60-90% of school children as well as a vast number of adults. The aim of this work was to define patterns of progression of the disease based on longitudinal data in contrast to using a cross-sectional assessment. dmft/DMFT scores were collected at ages 5, 12, 14, 16, 17, and 18 from 876 individuals. We tested our newly defined phenotypes for association with genetic variants in genes shown to be associated with caries. We generated genotyping data using Taqman chemistry in markers of genes involved in processes such as enamel formation and salivary contributions. Kallikrein 4 (KLK4) was found to show a significant association with the created phenotypes (p = 0.0008 in a recessive model for low caries experience in the primary dentition vs. high caries experience in the primary dentition, and p = 0.0004 in a recessive model for caries free primary dentition vs. high caries experience in the primary dentition).

Objectives: To evaluate prevalence, distribution, and sexual dimorphism of dental anomalies (DA) among different skeletal malocclusions (SM) and growth patterns (GP) under the hypothesis that specific clinical patterns exist and may indicate common etiological roots. Materials and Methods: A total of 1047 orthodontic records of patients older than 8 years were evaluated. The SN-GoGn angle was used to classify GP (hypodivergent, normal, and hyperdivergent), and the ANB angle was used to verify SM (Angle Classes I, II, and III). These assessments were done from lateral cephalometric radiographs. DA were diagnosed using panoramic radiographs by one calibrated investigator. Odds ratios, chi-square, and Student's t-tests were used. Results: Of the subjects, 56.7% were female, with mean age of 16.41 (±10.61) years. The prevalence of DA was 15.7%. Impaction and tooth agenesis were the most prevalent DA, with relative frequencies of 14.4% and 9.7%, respectively. DA were most prevalent in Class III SM (80.8%) and in hypodivergent GP (82.5%), although this was not statistically significant. Tooth agenesis (P < .01) and microdontia (P = .025) were significantly more common among hypodivergent GP and Class III SM, respectively. Conclusions: The results of this study support the idea that DA are preferentially associated with certain patterns of malocclusion.

Although children with oral clefts have a higher risk for dental anomalies when compared with the general population, prior studies have shown conflicting results regarding their dental decay risk. Also, few studies have assessed dental decay risk in unaffected relatives of children with clefts. Thus, the question of increased risk of dental decay in individuals with oral clefts or their unaffected relatives is still open for empirical investigation. This study characterizes dental decay in the largest international cohort to date of children with nonsyndromic clefts and their relatives, as compared with controls, and it addresses whether families with oral clefts have a significantly increased risk for dental decay versus the general population. A total of 3,326 subjects were included: 639 case probands, 1,549 unaffected relatives, and 1,138 controls. Decay was identified from in-person dental examinations or intraoral photographs. Case-control differences were tested with regression analysis. No significant differences were shown in percentage decayed and filled teeth and decayed teeth in the primary dentition (dft, dt) and permanent dentition (DFT, DT) in cases versus controls. In the cleft region, no significant differences were seen in primary or permanent decay (dt, DT) when compared with controls. No difference was found with regard to cleft type and percentage dft, dt, DFT, and DT in case probands. Nonsignificant differences were found in unaffected siblings and parents versus controls (primary and permanent dentitions). Collectively, these findings indicate that individuals with nonsyndromic oral clefts and their families do not have a higher dental decay risk as compared with the general population. These results suggest that either genetic or environmental factors underlying a higher susceptibility for dental anomalies do not increase caries risk or that the seemingly higher risk for dental decay associated with increased dental anomalies in case probands may be superseded by possible greater access to dental care.

Our goal was to verify the association between candidate polymorphisms and skeletal Class III malocclusion in a well-characterized homogeneous sample set.Thirty-five single-nucleotide polymorphisms were studied from 10 candidate loci in 54 Class III subjects and 120 controls. Skeletal Class III characteristics included ANB angle less than 0°, SNB angle greater than 83° (mandibular prognathism), SNA angle less than 79° (maxillary deficiency), Class III molar relationship, and negative overjet. Inclusion criteria for the controls were ANB angle between 0° and 4°, Class I molar relationship, and normal overjet. Chi-square and Fisher exact tests and principal component (PC) analysis were used to determine overrepresentation of marker alleles with alpha of 0.05. Odds ratios and 95% confidence intervals were calculated.MYO1H (rs10850110 AG) (P 0.01; odds ratio, 7.44 [4.02-13.77]) was associated with an increased risk for the mandibular prognathism phenotype. These results were confirmed by PC analysis, which showed 4 PCs representing the sample variations (PC1, 37.24%; PC2, 20.02%; PC3, 12.18%; and PC4, 11.40%), and PC1 was associated with MYO1H (P 0.001). We also found by PC analysis associations between MYO1H (P 0.001) and GHR (rs2973015 AG) (P = 0.001) with PC2 and between FGF10 (rs593307 AG) (P = 0.001) with PC4.Polymorphism in MYO1H could be used as a marker for genetic susceptibility to Class III malocclusion with mandibular prognathism, and polymorphisms in GHR and FGF were associated with maxillomandibular discrepancies. This study may contribute to improved diagnosis and further research assessing possible differences in treatment responses based on genetic polymorphisms.

Saliva components play a crucial role in the integrity of the dental enamel and in caries susceptibility. The saliva characteristics are controlled by many factors, including genetic factors. Therefore, this study aimed to evaluate the association between the genetic variations in genes expressed in enamel development with calcium and phosphorus levels in saliva. We collected 276 unrelated 12-year-old children from private and public schools. Saliva was collected for DNA extraction from oral cells and for measurement of calcium and phosphorus. Inductively coupled plasma-mass spectrometry determined calcium and phosphorus levels in whole saliva. Fifteen genetic variations in 9 genes were analyzed. The genotype was determined by real-time polymerase chain reactions. Data were analyzed using Plink with an alpha of 5%. Genetic variations in AMELX, AMNB and ESRRB were associated with the calcium level in saliva (p < 0.05). A borderline association was observed in ENAM allele distribution shown with phosphate level in saliva (p = 0.049). In conclusion, our results are the first to report that genetic variations contribute to calcium and phosphorus levels in saliva.

AIMS There are many factors that play into the success or failure of dental treatments, and mental health has been hypothesized to increase failure rates in treatment such as resin-based restorations. The goal of this work was to evaluate if composite resin dental restorations perform the same in individuals with depression in comparison to matched individuals without depression. METHODS AND RESULTS A total of 6,026 individuals from the University of Pittsburgh Dental Registry and DNA Repository project were evaluated and 326 patients with depression were selected for this study. They were matched by age, sex, ethnicity, and smoking history with 326 subjects without depression. Rates of failure of resin-based restorations were determined in both groups. Chi-square was used for all comparisons with alpha set at 0.05. We found significantly higher failure rates of resin-based restorations in patients diagnosed with clinical depression (p < 0.00001, OR = 1.89, 95% C.I. 1.6 to 2.23). DISCUSSION The significantly higher failure rates in patients with clinical depression suggests that clinical depression has an effect on the success of resin-based restorations. The results of this study suggest a need for more personalized dental care for patients, which includes taking into account their mental health and its subsequent effects on oral health and hygiene, and customized definitions of follow-up time intervals.

BACKGROUND To evaluate whether genetic polymorphisms in FGF3, FGF10, and FGF13 are associated with temporomandibular disorders (TMD) in patients that presented dentofacial deformities requiring orthognathic surgery. MATERIAL AND METHODS The sample comprised a total of 113 patients of both sexes. The diagnosis of TMD was performed before orthognathic surgery between Research Diagnostic Criteria for Temporomandibular Disorders (RDC-TMD). According to the TMD assessment, the patients were divided into 3 major groups: myofascial pain, articular disc displacements and other TMD conditions (arthralgia, arthritis, and arthrosis). Genomic DNA was collected from saliva samples and genetic polymorphisms in FGF3 (rs1893047 and rs7932320), FGF10 (rs900379) and FGF13 (rs5931572 and rs5974804) were analyzed by real-time polymerase chain reactions. The association between the TMD conditions and the genetic polymorphisms assessed were analyzed by Poisson Regression. The model was calculated on bivariate and adjusted by sex. The established alpha was 5%. Data were analyzed by using SPSS software (IBM, Armonk, NY). RESULTS The genetic polymorphisms rs7932320 in FGF3 (P

Aquaporins (AQPs) are membrane channels that provide for transport of water and other small molecules across the lipid bilayer of cells. Their function is essential for physiologic processes such as cell volume regulation, chondrocyte hypertrophy during appendicular skeletal growth, water reabsorption in the kidney tubules, and water excretion by the salivary glands. The ten AQP isoforms show tissue specificity and are involved in different pathologies and inflammatory diseases. This study addresses the hypothesis that arthritis, periodontitis, and temporomandibular joint disorders (TMDs) can be influenced by variation in the AQP genes at 12q13.12 locus. Salivary samples of 688 individuals were obtained from the Dental Registry and DNA Repository project at the University of Pittsburgh. Ten polymorphisms in four AQP genes (AQP1, 2, 5, and 6) were genotyped and correlated to disease status as reported by patients. Associations were found between the single nucleotide polymorphism (SNP) rs467323 in AQP2 and TMD in both genotypic (p = 0.03) and recessive (p = 0.02) models, and between rs1996315 in AQP6 and periodontitis (p = 0.05). Combined analysis of TMD and periodontitis showed an association with rs3741559 in AQP2 (p = 0.02). When conducting haplotype analysis of rs467323 and rs10875989 in AQP2, the haplotype CT showed an association with the TMD phenotype (p = 0.007). Our results suggest that the aquaporin locus at 12q13.12 may contribute to the pathogenesis of inflammatory conditions such as periodontitis and TMD. Thus, oral and skeletal health are correlated and potential susceptibility screening strategies may be developed.

Single nucleotide polymorphisms (SNPs) in WNT genes may impact gene/protein function and contribute to individual predisposition to apical periodontitis (AP). Here, we investigated the association of SNPs in/nearby WNT3, WNT3A, WNT5A, WNT8A, WNT9B and WNT11 genes with AP using a case-control dataset. Cases were defined as individuals with deep caries and AP (n = 188); controls had deep caries and no AP (n = 230). Genotyping was performed using Taqman chemistry in real time PCR. Data analyses was performed using Fisher Exact tests assuming a Bonferroni correction threshold value of 0.005. Single-SNP association analysis revealed a trend for association with WNT3 rs9890413 genotypes (P = 0.009) under a dominant model and allelic association for WNT3A rs1745420 (P = 0.009). Haplotypes involving WNT3-WNT9B-WNT3A alleles were also significantly associated with AP (P ≤ 0.003). Luciferase reporter assays showed higher transcriptional activity (1.4-fold) with the alternate G allele in rs1745420. Expression of WNT3, WNT3A and WNT5A in AP tissues was significantly higher than in control tissues, and inversely correlated with the expression of SERPINB1, COL1A1 and TIMP1 (P

Smoking is a leading cause of preventable death. The effect of tobacco is even more contundent in people with mental illness and, in general, cigarette smoking addiction is influenced by genetic factors. The opioid system is involved in the mesolimbic reward system, which is of great importance in addictive behaviors, such as smoking and is influenced by genes such as the OPRM1. The aim of this study was to evaluate if selecting a comparison group that include light smokers versus people that never smoked impacts the results of genetic association studies. In addition, to evaluate the genetic association in different groups of smokers by analyzing independent covariates such as mental illness and clinical dental data. All subjects were participants of the Dental Registry and DNA Repository project. Genotyping was carried out using TaqMan chemistry for two markers in OPRM1 (rs553202 and rs7755635). Logistic regression analyses were performed as implemented in PLINK. The established value for alpha was 5%, and the Hardy-Weinberg equilibrium was evaluated by the chi-square test with one degree of freedom for each marker. 1,897 patients were included, which were allocated to eight distinct groups, according to the frequency and quantity of cigarettes smoked and mental illness status. There was no significant association between the two markers in OPRM1 and smoking. When mental illness and dental clinical data (tooth loss, dental caries, and periodontitis) were used as covariates, there were associations between heavy smoking and OPRM1, when non-smokers were used as comparison. We did not have diet or microbiome data to consider for these dental analyses and suggest that these kinds of data should be always incorporated in the future. Significant results were found only when the covariables mental illness and oral clinical data were added to the analysis.

Molar incisor hypomineralization (MIH) is an enamel condition characterized by lesions ranging in color from white to brown which present rapid caries progression, and mainly affects permanent first molars and incisors. These enamel defects usually occur when there are disturbances during the mineralization or maturation stage of amelogenesis. Both genetic and environmental factors have been suggested to play roles in MIH’s development, but no conclusive risk factors have shown the source of the disease. During head and neck development, the interferon regulatory factor 6 (IRF6) gene is involved in the structure formation of the oral and maxillofacial regions, and the transforming growth factor alpha (TGFA) is an essential cell regulator, acting during proliferation, differentiation, migration and apoptosis. In this present study, it was hypothesized that these genes interact and contribute to predisposition of MIH. Environmental factors affecting children that were 3 years of age or older were also hypothesized to play a role in the disease etiology. Those factors included respiratory issues, malnutrition, food intolerance, infection of any sort and medication intake. A total of 1,065 salivary samples from four different cohorts were obtained, and DNA was extracted from each sample and genotyped for nine different single nucleotide polymorphisms. Association tests and logistic regression implemented in PLINK were used for analyses. A potential interaction between TGFA rs930655 with all markers tested in the cohort from Turkey was identified. These interactions were not identified in the remaining cohorts. Associations (p

Dentofacial deformities are dys-morpho-functional disorders involving the temporomandibular joints (TMJ). Many authors have reported a TMJ improvement in dysfunctional subjects with malocclusion after orthodontic or combined orthodontic and surgical treatment particularly for the relief of pain. In particular, few studies have highlighted the demographic and clinical predictors of response to surgical treatment. To date, no genetic factor has yet been identified as a predictor of response to surgical treatment. The aim of this cohort study is therefore to identify single-nucleotide polymorphisms associated with postoperative temporomandibular disorders (TMD) or with TMJ symptoms after orthognathic surgery. Here, we found the AA genotype of SNP rs1643821 (ESR1 gene) as a risk factor for dysfunctional worsening after orthognathic surgery. In addition, we have identified TT genotype of SNP rs858339 (ENPP1 gene) as a protective factor against TMD in a population of patients with dentofacial deformities. Conversely, the heterozygous genotype AT was identified as a risk factor of TMD with respect to the rest of our population. All these elements are particularly important to bring new screening strategies and tailor future treatment. Perspective This study allows us to identify sub-populations at high risk of developing postoperative temporomandibular disorders after orthognathic surgery procedures. Many other genes of interest could be potential factors influencing the dysfunctional response to orthognathic surgery, particularly genes of the Opera cohort.

Despite the success of osseointegrated implants, failures have increased significantly, associated with development of peri-implantitis. Multiple factors influence the peri-implant bone loss, including environmental and genetic causes. BMPs (Bone morphogenetic proteins) are growth factors that induce bone formation. FGF (fibroblast growth factors) and their receptors (FGFRs) play important roles by controlling the levels of cell proliferation, differentiation and migration. BMP/FGF relationship is responsible for promoting bone regeneration and bone loss. The aim of this study was to analyze the correlation between BMP4, FGF3, FGF10 and FGFR1 genes and peri-implant bone loss. Two hundred and fifteen volunteers, with 754 dental implants, were submitted to oral examination and divided in healthy group (n=129) and peri-implantitis group (n=86). Thirteen polymorphisms in BMP4, FGF3, FGF10 and FGFR1 genes were analyzed individually and in haplotype. The chi-square test correlated genotypes, allelic and haplotype frequencies. Values of p

Molar-incisor hypomineralization (MIH) is a condition that is defined based on its peculiar clinical presentation. Reports on the etiology of the condition and possible risk factors are inconclusive and the original suggestion that MIH is an idiopathic condition is often cited. Our group was the first to suggest MIH has a genetic component that involves genetic variation in genes expressed during dental enamel formation. In this report, we provide a rationale to explain the preferential affection of molars and incisors. We suggest that MIH is a genetic condition based on its prevalence, which varies depending on the geographic location, and the evidence that on occasion second primary molars, permanent canines, and premolars can show signs of hypomineralization of enamel when molars and incisors are affected.

The aim of this study was to investigate the association between condylar bone morphological characteristics with occlusal conditions. Besides the study will compare the tomography images with the real condition in 122 temporomandibular joints from 61 skulls. The occlusal conditions were evaluated by number of teeth missing, measurement of overjet and overbite, in millimeters, and presence or absence of crossbite, openbite and dental rotation. The condylar bone morphological conditions were classified in five types (normal, presence of erosion, presence of osteophytes, flattening and/or deformation). This classification was used in real skulls and in Cone Beam Computed tomography (CBCT) images. The data were submitted to statistical analysis with a level of significance of 0.05. Occlusal variables have no association to morphologic data (p > 0.05). Normal condylar bone was seen in 62 CBCT versus 53 in real skulls while morphological alterations were seen in 60 CBCT versus 67-real condyles. The clinical and tomographic measurements were compared, demonstrating an important difference in the classification demonstrating poor association between detection methods (k − 0.3, p

Background There is concern that fluorides in the drinking water is hazardous to health. Methods We conducted an observational study in the village of Hanliyenice (population 280), Turkey, which has 2.5 times higher than optimal levels of fluoride in the drinking water and evaluated all children 7–13 years of age (N = 30). We collected information on dental decay, fluorosis, daily water consumption and diet, child history and her family history of cancer, cardiovascular risks/diseases, and asthma, and obtained a blood sample for extraction of genomic DNA. We genotyped ten single nucleotide polymorphisms in aquaporins. Results As expected, a high number of children were dental caries free (19 out of 30) and had fluorosis (25 out of 30). Family history of cancer, cardiovascular events, and asthma was not different from the expected figures based on Turkey. One variant just upstream of AQP5 was associated with being fluorosis free. (G allele of AQP5 rs296763, p = 6.0E−6). Conclusions Exposure to levels of fluoride twice as high than the optimum in the drinking water increases the prevalence of fluorosis, dramatically decreases dental caries, and does not increase the risk of cancer, cardiovascular events, and asthma.

BACKGROUND Oestrogen (ES) and growth hormone (GH) are hormones that may have a role in caries aetiology and developmental defects of enamel (DDE) since their receptors (ERs and GHR) are expressed during amelogenesis. AIM To evaluate whether genetic polymorphisms in the genes that codify the ERα (ESR1) and GHR are associated with caries experience and DDE in children. DESIGN Two hundred and sixteen children of both genders, aged 9-12 years, were examined and classified according to caries and DDE phenotype. Genomic DNA was extracted from buccal cells in saliva. Genetic polymorphisms in ERS1 (rs1884051 and rs12154178) and GHR (rs297305, rs2940913, rs2910875, and rs1509460) were genotyped using TaqMan chemistry. Data were analysed by PLINK, while the chi-square test was used to compare allele and genotype distributions (alpha of 5%). RESULTS A total of 131 children (60.7%) had caries experience, and 43 (19.9%) presented DDE. Genotype and allele distributions were not associated with caries experience (P > 0.05). Genotype and allele distributions between DDE, affected and unaffected, were associated with the polymorphism rs12154178 in ESR1 (P = 0.01 and P = 0.001, respectively) and with the polymorphism rs1509460 in GHR (P = 0.05 and P = 0.02, respectively). CONCLUSIONS Genetic polymorphisms in ERS1 (rs12154178) and GHR (rs1509460) are associated with DDE.

Nonsyndromic cleft lip with or without cleft palate (NSCL/P) is the most common craniofacial birth defect in humans and is notable for its apparent sexual dimorphism where approximately twice as many males are affected as females. The sources of this disparity are largely unknown, but interactions between genetic and sex effects are likely contributors. We examined gene-by-sex (G x S) interactions in a worldwide sample of 2,142 NSCL/P cases and 1,700 controls recruited from 13 countries. First, we performed genome-wide joint tests of the genetic (G) and G x S effects genome-wide using logistic regression assuming an additive genetic model and adjusting for 18 principal components of ancestry. We further interrogated loci with suggestive results from the joint test (p < 1.00 × 10(−5)) by examining the G x S effects from the same model. Out of the 133 loci with suggestive results (p < 1.00 × 10(−5)) for the joint test, we observed one genome-wide significant G x S effect in the 10q21 locus (rs72804706; p = 6.69 × 10(−9); OR = 2.62 [1.89, 3.62]) and 16 suggestive G x S effects. At the intergenic 10q21 locus, the risk of NSCL/P is estimated to increase with additional copies of the minor allele for females, but the opposite effect for males. Our observation that the impact of genetic variants on NSCL/P risk differs for males and females may further our understanding of the genetic architecture of NSCL/P and the sex differences underlying clefts and other birth defects.

Previously reported co-occurrence of colorectal cancer (CRC) and tooth agenesis (TA) and the overlap in disease-associated gene variants suggest involvement of similar molecular pathways. Here, we took an unbiased approach and tested genome-wide significant CRC-associated variants for association with isolated TA. Thirty single nucleotide variants (SNVs) in CRC-predisposing genes/loci were genotyped in a discovery dataset composed of 440 individuals with and without isolated TA. Genome-wide significant associations were found between TA and ATF1 rs11169552 (P = 4.36 × 10−10) and DUSP10 rs6687758 (P = 1.25 × 10−9), and positive association found with CASC8 rs10505477 (P = 8.2 × 10−5). Additional CRC marker haplotypes were also significantly associated with TA. Genotyping an independent dataset consisting of 52 cases with TA and 427 controls confirmed the association with CASC8. Atf1 and Dusp10 expression was detected in the mouse developing teeth from early bud stages to the formation of the complete tooth, suggesting a potential role for these genes and their encoded proteins in tooth development. While their individual contributions in tooth development remain to be elucidated, these genes may be considered candidates to be tested in additional populations.

Orofacial clefts (OFCs) are common, complex birth defects with extremely heterogeneous phenotypic presentations. Two common subtypes—cleft lip alone (CL) and CL plus cleft palate (CLP)—are typically grouped into a single phenotype for genetic analysis (i.e., CL with or without cleft palate, CL/P). However, mounting evidence suggests there may be unique underlying pathophysiology and/or genetic modifiers influencing expression of these two phenotypes. To this end, we performed a genome-wide scan for genetic modifiers by directly comparing 450 CL cases with 1,692 CLP cases from 18 recruitment sites across 13 countries from North America, Central or South America, Asia, Europe, and Africa. We identified a region on 16q21 that is strongly associated with different cleft type (P = 5.611 × 10−8). We also identified significant evidence of gene–gene interactions between this modifier locus and two recognized CL/P risk loci: 8q21 and 9q22 (FOXE1) (P = 0.012 and 0.023, respectively). Single nucleotide polymorphism (SNPs) in the 16q21 modifier locus demonstrated significant association with CL over CLP. The marker alleles on 16q21 that increased risk for CL were found at highest frequencies among individuals with a family history of CL (P = 0.003). Our results demonstrate the existence of modifiers for which type of OFC develops and suggest plausible elements responsible for phenotypic heterogeneity, further elucidating the complex genetic architecture of OFCs. Fil: Carlson, Jenna C.. University of Pittsburgh; Estados Unidos Fil: Standley, Jennifer. University of Iowa; Estados Unidos Fil: Petrin, Aline. University of Iowa; Estados Unidos Fil: Shaffer, John R.. University of Pittsburgh; Estados Unidos Fil: Butali, Azeez. University of Iowa; Estados Unidos Fil: Buxó, Carmen J.. Universidad de Puerto Rico; Puerto Rico Fil: Castilla, Eduardo Enrique. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Parque Centenario. CEMIC-CONICET. Centro de Educaciones Médicas e Investigaciones Clínicas "Norberto Quirno". CEMIC-CONICET.; Argentina Fil: Christensen, Kaare. University of Southern Denmark; Dinamarca Fil: Deleyiannis, Frederic W.-D.. State University of Colorado Boulder; Estados Unidos Fil: Hecht, Jacqueline T.. University of Texas; Estados Unidos Fil: Field, L. Leigh. University of British Columbia; Canadá Fil: Garidkhuu, Ariuntuul. Tohoku University; Japón. Mongolian National University Of Medical Sciences; Mongolia Fil: Moreno Uribe, Lina M.. University of Iowa; Estados Unidos Fil: Nagato, Natsume. Aichi Gakuin University; Japón Fil: Orioli, Ieda M.. Instituto Nacional de Genética Médica Populacional; Brasil. Universidade Federal do Rio de Janeiro; Brasil Fil: Padilla, Carmencita. University Of The Philippines Manila; Filipinas Fil: Poletta, Fernando Adrián. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Parque Centenario. CEMIC-CONICET. Centro de Educaciones Médicas e Investigaciones Clínicas "Norberto Quirno". CEMIC-CONICET.; Argentina Fil: Suzuki, Satoshi. Aichi Gakuin University; Japón Fil: Vieira, Alexandre R.. University of Pittsburgh at Johnstown; Estados Unidos. University of Pittsburgh; Estados Unidos Fil: Wehby, George. University of Iowa; Estados Unidos Fil: Weinberg, Seth M.. University of Pittsburgh; Estados Unidos. University of Pittsburgh at Johnstown; Estados Unidos Fil: Beaty, Terri H.. University Johns Hopkins; Estados Unidos Fil: Feingold, Eleanor. University of Pittsburgh; Estados Unidos Fil: Murray, Jeffrey C.. University of Iowa; Estados Unidos Fil: Marazita, Mary L.. University of Pittsburgh; Estados Unidos. University of Pittsburgh at Johnstown; Estados Unidos Fil: Leslie, Elizabeth J.. University of Emory; Estados Unidos

Children with oral clefts show a wide range of dental anomalies, adding complexity to understanding the phenotypic spectrum of orofacial clefting. The evidence is mixed, however, on whether the prevalence of dental anomalies is elevated in unaffected relatives and is mostly based on small samples. In the largest international cohort to date of children with nonsyndromic clefts, their relatives, and controls, this study characterizes the spectrum of cleft-related dental anomalies and evaluates whether families with clefting have a significantly higher risk for such anomalies compared with the general population. A total of 3,811 individuals were included: 660 cases with clefts, 1,922 unaffected relatives, and 1,229 controls. Dental anomalies were identified from in-person dental exams or intraoral photographs, and case-control differences were tested using χ2 statistics. Cases had higher rates of dental anomalies in the maxillary arch than did controls for primary (21% vs. 4%, P = 3 × 10−8) and permanent dentitions (51% vs. 8%, P = 4 × 10−62) but not in the mandible. Dental anomalies were more prevalent in cleft lip with cleft palate than other cleft types. More anomalies were seen in the ipsilateral side of the cleft. Agenesis and tooth displacements were the most common dental anomalies found in case probands for primary and permanent dentitions. Compared with controls, unaffected siblings (10% vs. 2%, P = 0.003) and parents (13% vs. 7%, P = 0.001) showed a trend for increased anomalies of the maxillary permanent dentition. Yet, these differences were nonsignificant after multiple-testing correction, suggesting genetic heterogeneity in some families carrying susceptibility to both overt clefts and dental anomalies. Collectively, the findings suggest that most affected families do not have higher genetic risk for dental anomalies than the general population and that the higher prevalence of anomalies in cases is primarily a physical consequence of the cleft and surgical interventions.

ObjectiveThe aim of this work was to fine-map the region 6q23.1, which obtained suggestive linkage signal (logarithm of the odds [LOD] score = 2.22 under a recessive model) to cleft lip with or without cleft palate (CL±P) in our previous genome-wide linkage scan to identify possible genetic variants that may contribute to CL±P.DesignWe used densely spaced markers spanning the entire 6q23.1 region to test for association with CL±P in a family cohort sample.SettingClinical information and DNA samples were obtained from families in the Philippines at their homes or primary health care clinics.ParticipantsThe study sample consisted of 477 subjects (224 females and 253 males), segregating isolated CL±P, from 72 living in the same area in the Philippines.Main Outcome MeasureOvertransmission of alleles to persons born with CL±P.ResultsWe found statistical evidence of association between a marker of TULP4 (rs651333) with CL±P ( P = .00007).ConclusionsOur results further support the linkage results for the chromosome 6q region and reveal a novel candidate gene for CL±P.

Dental caries (tooth decay) is the most common chronic disease, worldwide, affecting most children and adults. Though dental caries is highly heritable, few caries-related genes have been discovered. We investigated whether 18 genetic variants in the group of non-amelogenin enamel matrix genes (AMBN, ENAM, TUFT1, and TFIP11) were associated with dental caries experience in 13 age- and race-stratified samples from six parent studies (N = 3,600). Linear regression was used to model genetic associations and test gene-by-fluoride interaction effects for two sources of fluoride: daily tooth brushing and home water fluoride concentration. Meta-analysis was used to combine results across five child and eight adult samples. We observed the statistically significant association of rs2337359 upstream of TUFT1 with dental caries experience via meta-analysis across adult samples (p

Introduction α-Actinins are myofibril anchor proteins that influence the contractile properties of skeletal muscles. ACTN2 is expressed in slow type I and fast type II fibers, whereas ACTN3 is expressed only in fast fibers. ACTN3 homozygosity for the 577X stop codon (ie, changing 577RR to 577XX, the R577X polymorphism) results in the absence of α-actinin-3 in about 18% of Europeans, diminishes fast contractile ability, enhances endurance performance, and reduces bone mass or bone mineral density. We have examined ACTN3 expression and genetic variation in the masseter muscle of orthognathic surgery patients to determine the genotype associations with malocclusion. Methods Clinical information, masseter muscle biopsies, and saliva samples were obtained from 60 subjects. Genotyping for ACTN3 single nucleotide polymorphisms, real-time polymerase chain reaction quantitation of muscle gene message, and muscle morphometric fiber type properties were compared to determine statistical differences between genotype and phenotype. Results Muscle mRNA expression level was significantly different for ACTN3 single nucleotide polymorphism genotypes ( P ACTN3 genotypes was significantly different for the sagittal and vertical classifications of malocclusion, with the clearest association being elevated 577XX genotype in skeletal Class II malocclusion ( P = 0.003). This genotype also resulted in significantly smaller diameters of fast type II fibers in masseter muscles ( P = 0.002). Conclusion ACTN3 577XX is overrepresented in subjects with skeletal Class II malocclusion, suggesting a biologic influence during bone growth. ACTN3 577XX is underrepresented in subjects with deepbite malocclusion, suggesting that muscle differences contribute to variations in vertical facial dimensions.

Cleft lip and palate is the most common craniofacial birth defect, and its etiology has been the focus of many reports in the literature. It is well accepted that both genetics and environment play a role in the condition; however, the authors still have not been able to translate what have been learned into clinical applications. This paper provides an interpretation of 2 possible mechanisms leading to cleft lip and palate in humans. First, the authors reflect on the known association between maternal cigarette smoking and risk for cleft lip and palate and the proposed hypoxic mechanism put forward to explain this association. Second, the authors reflect on the difference in frequency between left and right cleft lip and propose that without more extensive clinical definitions, it will be difficult to definitely unveil genetic targets that can be used for counseling.

Objectives To evaluate the association between hypoxia during embryo development and oral clefts in an animal model, and to evaluate the association between polymorphisms in the HIF-1A gene with oral clefts in human families. Material and Methods The study with the animal model used zebrafish embryos at 8 hours post-fertilization submitted to 30% and 50% hypoxia for 24 hours. At 5 days post-fertilization, the larvae were fixed. The cartilage structures were stained to evaluate craniofacial phenotypes. The family-based association study included 148 Brazilian nuclear families with oral clefts. The association between the genetic polymorphisms rs2301113 and rs2057482 in HIF-1A with oral clefts was tested. We used real time PCR genotyping approach. ANOVA with Tukey's post-test was used to compare means. The transmission/disequilibrium test was used to analyze the distortion of the inheritance of alleles from parents to their affected offspring. Results For the hypoxic animal model, the anterior portion of the ethmoid plate presented a gap in the anterior edge, forming a cleft. The hypoxia level was associated with the severity of the phenotype (p0.05). Conclusion Hypoxia is involved in the oral cleft etiology, however, polymorphisms in HIF-1A are not associated with oral clefts in humans.

The aim of this study was to evaluate whether genetic polymorphisms in AMELX, AMBN, ENAM, TFIP11, and TUFT1 genes are associated with dental fluorosis (DF). A total of 1,017 children from 2 Brazilian cohorts were evaluated. These populations lived in cities with fluoridation of public water supplies. DF was assessed in erupted permanent teeth using the modified Dean index. The polymorphisms rs946252, rs12640848, rs4694075, rs5997096, and rs4970957 were analyzed by real-time PCR from genomic DNA. Associations between DF, genotype, and allele distribution were evaluated using the χ2 test, with an alpha of 5%. The polymorphisms rs4694075, rs5997096, and rs4970957 in AMBN, TFIP11, and TUFT1 were associated with DF (p < 0.05). In conclusion, enamel matrix genes are associated with DF.

Purpose Bone remodeling is essential in maintaining bone health. Considering that ENPP1 contributes to bone geometry and bone mineralization, the aim of our study was to analyze the association between single-nucleotide polymorphisms (SNPs) of ENPP1 and condylar remodeling. Materials and methods A total of 156 patients undergoing orthodontic and maxillofacial surgery treatment for correction of malocclusion were included in this prospective study. Saliva samples from all subjects were used for DNA extraction and genotyping. Four ENPP1 SNP s were selected and tested to determine whether specific allelic variants are correlated with condylar remodeling. The criteria of condylar remodeling chosen were the ratio between each side of condylar height or surface differences on a dental panoramic of each patient. A diagnostic threshold was set at 15% difference between both sides. Results The ENPP1 SNP rs9373000 showed a statistically significant association with condylar height ratio >15% (p = 0.012). The GG genotype was found to be a protective factor against condylar height decrease (p = 0.003). Conclusion This study identifies the genetic variant rs9373000 as a potentially causal variant for mandibular condyle geometry variation for patients presenting with dento-facial deformities.

Objective Type I myosins are molecular motors necessary for glucose transport in the cytoplasm and initiation of transcription in the nucleus. Two of these, MYO1H and MYO1C , are paralogs which may be important in the development of malocclusion. The objective of this study was to investigate their gene expression in the masseter muscle of malocclusion subjects. Two functionally related proteins known to contribute to malocclusion were also investigated: KAT6B (a chromatin remodelling epigenetic enzyme which is activated by MYO1C ) and RUNX2 (a transcription factor regulating osteogenesis which is activated by KAT6B ). Design Masseter muscle samples and malocclusion classifications were obtained from orthognathic surgery subjects. Muscle was sectioned and immunostained to determine fibre type properties. RNA was isolated from the remaining sample to determine expression levels for the four genes by TaqMan ® RT-PCR. Fibre type properties, gene expression quantities and malocclusion classification were compared. Results There were very significant associations ( P MYO1C and KAT6B expressions. There were also significant associations ( P RUNX2 expression and masseter muscle type II fibre properties. Very few significant associations were identified between MYO1C and masseter muscle fibre type properties. Conclusions The relationship between MYO1C and KAT6B suggests that the two are interacting in chromatin remodelling for gene expression. This is the nuclear myosin1 (NM1) function of MYO1C. A surprising finding is the relationship between RUNX2 and type II masseter muscle fibres, since RUNX2 expression in mature muscle was previously unknown. Further investigations are necessary to elucidate the role of RUNX2 in adult masseter muscle.